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High maternal thyroid levels raised risk for adverse neonatal outcomes
The link between maternal thyroid parameters and adverse fetal and neonatal outcomes has been established in the literature. In a recent study, researchers in Rotterdam, the Netherlands, suggest that maternal high-normal free thyroxine levels in early pregnancy are linked to lower birth weight and increased risk for small size for gestational age at birth.
They utilized data from women with a delivery date from April 2002 to January 2006 in the Generation R Study, a population-based cohort from early fetal life and beyond.
Serum thyroid-stimulating hormone, free T4 and thyroid peroxidase antibody levels were measured early in 4,464 pregnant women at a mean of 13.3 weeks, researchers wrote. Cord serum TSH and free T4 levels were also measured in 2,724 newborns at a mean of 39.9 weeks. Small size for gestational age at birth (SGA) was defined as a gestational age-adjusted birth weight below the 2.5th percentile. Low birth weight (LBW) was defined as birth weight of less than 2,500 g.
According to data, higher maternal free T4 levels were associated with lower birth weight (P=1.6×10–5), and an increased risk for SGA newborns (OR=1.09; 95% CI, 1.01-1.17) in mothers with normal-range free T4 and TSH levels. Further data indicate birth weight was linked to cord TSH (P=.007) and free T4 levels (P=9.2×10–13).
In an accompanying editorial, Tuija Männistö, MD, PhD, of the division of epidemiology in biostatistics and prevention research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Md., wrote that lowering the free T4 reference intervals in pregnant women or screening all pregnant women for free T4 cannot be recommended.
“We are accumulating evidence on defining normal TSH levels during pregnancy, but even there we have many unanswered questions, especially regarding the treatment of subclinical hypothyroidism in preventing adverse pregnancy and neonatal outcomes,”Männistö wrote.
However, Männistö added that Medici and colleagues’ recent study is a step in the right direction. She suggests randomized and observational studies beginning before pregnancy, as well as longitudinal serum samples during pregnancy.
For more information:
Männistö T. J Clin Endocrinol Metab. 2013;98:43-44.
Medici M. J Clin Endocrinol Metab. 2013;98:59-66.
Disclosure:The researchers report no relevant financial disclosures. Männistö reports no relevant financial disclosures.
Perspective
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In a study which evaluated 4,464 pregnant Dutch women, Medici et al reported a significant association between high-normal free T4 levels (with normal TSH values) in the 13th week of pregnancy and lower birth weight in their offspring. Similar results were reported in a study performed by Shields et al in which 616 women from the UK were evaluated at 28 weeks gestation. If low birth weight is associated with high free normal thyroxine levels in women with a normal TSH, a similar, if not more robust finding would be expected in pregnant women with subclinical hyperthyroidism. Yet, in a prospective cohort of 25,765 American women, Casey and colleagues found no association between subclinical hyperthyroidism and birth weight in the offspring. Possible reasons for the disparate findings in the three studies include the well described limitations of free thyroxine assays during pregnancy and the study design which, in each of the investigations, evaluated free thyroxine levels at only one time point during pregnancy. Clarification of this issue requires a prospective study in which free thyroxine measurements are performed multiple times during pregnancy utilizing the gold standard method. Until such a study is performed, it is premature to narrow free T4 reference ranges, or treat abnormal free T4 levels (let alone high normal free T4 levels), in women with TSH results within the normal pregnancy reference values.